Hydrochloric Acid → HCID 18957612, compound

In 15 ml of dry dimethoxyethane was dissolved 5.2 g of ethyl malonate, and to the solution was added 3.8 g of a 50% sodium hydride (dispersion in an oil) with stirring under ice-cooling. To the mixture was added a solution of 20 ml of dry dimethoxyethane containing 12.3 g of 2-fluorobenzyl bromide. The mixture was stirred for 1 hour at room temperature, and then heated under reflux for 16 hours. The reaction mixture was evaporated under reduced pressure, and to the residue was acidified by an addition of diluted hydrochloric acid. The acidic mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was purified by column chromatography (eluent: benzene) to obtain 8.6 g of ethyl bis(2-fluorobenzyl)malonate as a colorless oil. In a mixture of 20 ml of dimethyl sulfoxide and 1 ml of water was dissolved 8.6 g of ethyl bis(2-fluorobenzyl)malonate, and to the solution was added 4.4 g of lithium chloride. The mixture was heated at 190°-200° C. for 10 hours. After cooling, the reaction mixture was acidified by an addition of diluted hydrochloric acid. The acidic mixture was extracted with ethyl acetate, and the ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. In 50 ml of methanol was dissolved the residue, and to the solution was added 30 ml of a 2N-aqueous sodium hydroxide solution. The mixture was heated under reflux for 1 hour, and the reaction mixture was evaporated under reduced pressure. The residue was dissolved in water, and the solution was extracted with diethyl ether. The aqueous layer was acidified by an addition of hydrochloric acid, and the acidic mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: chloroform/methanol=15/1) to obtain 2.85 g of bis(2-fluorobenzyl)acetic acid as a white powder.

1. temperatureThe mixture was heated at 190°-200° C. for 10 hours
2. temperatureAfter cooling
3. extractionThe acidic mixture was extracted with ethyl acetate
4. washthe ethyl acetate layer was washed with water
5. dry with materialdried over anhydrous magnesium sulfate
6. customevaporated under reduced pressure
7. dissolutionIn 50 ml of methanol was dissolved the residue
8. additionto the solution was added 30 ml of a 2N-aqueous sodium hydroxide solution
9. temperatureThe mixture was heated
10. temperatureunder reflux for 1 hour
11. customthe reaction mixture was evaporated under reduced pressure
12. dissolutionThe residue was dissolved in water
13. extractionthe solution was extracted with diethyl ether
14. additionThe aqueous layer was acidified by an addition of hydrochloric acid
15. extractionthe acidic mixture was extracted with ethyl acetate
16. washThe ethyl acetate layer was washed with water
17. dry with materialdried over anhydrous magnesium sulfate
18. customevaporated under reduced pressure
19. customThe residue was purified by silica gel column chromatography (eluent: chloroform/methanol=15/1)

ORD record

ord-397e7e4760a34c6597303a3ac6aacf84

Source dataset

uspto-grants-1989_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04870183